The real-world early neuroprotective effects of oral citicoline combination in prodromal dementia

Abstract

Background/Objectives: Early intervention in the prodromal stages of dementia is a primary focus of contemporary research, as delaying clinical progression may have a substantial public health impact. Citicoline, an endogenous precursor of phosphatidylcholine and acetylcholine, has been proposed as a nutritional compound with potential relevance to multiple cognitive domains. However, real-world evidence regarding its specific contributions in prodromal dementia populations is limited. This study was conducted to examine cognitive, functional, and emotional outcomes associated with the use of an oral citicoline combined preparation in individuals with prodromal dementia and early Alzheimer’s type cognitive decline. Methods: This was a two-centre, retrospective, observational, real-world cohort study. A cohort of 100 patients receiving a combined oral citicoline preparation and 50 age-matched healthy controls were evaluated at baseline and followed for 6–9 months. Participants underwent comprehensive neuropsychological assessments that evaluated domains including executive function, attention, processing speed, working memory, visual-spatial and verbal memory, fluency, general cognition, and mood. Standardized instruments included Stroop indices, Trail Making Tests A/B, SDMT, SPART-based measures, SBST, fluency tasks, the Boston Naming Test, and MoCA. Statistical analyses included age-adjusted and education-level-stratified comparisons. Results: Use of the citicoline combined preparation was associated with improvements in several cognitive domains, including executive functions, processing speed, working memory, visual-spatial memory, and both semantic and episodic fluency (all p < 0.05). Functional memory scanning and global cognition also showed improvement over the observation period. Significant differences between groups were observed at baseline and follow-up for multiple cognitive indices (most p < 0.001). Mood outcomes were more favorable in the citicoline combined preparation group, with reductions in depressive and anxiety symptoms. Age-adjusted models identified age as an important covariate, and participants with lower educational levels demonstrated comparatively greater cognitive gains. Conclusions: In this real-world observational study, use of an oral citicoline combined preparation was associated with multidomain improvements in cognitive and mood-related outcomes in individuals with prodromal dementia/early Alzheimer-type decline. Given the observational design, these findings should be considered exploratory and require confirmation in prospective randomised controlled trials. © 2026 by the authors.